This longitudinal study of intravenous drug users (IVDU) in New Haven, Connecticut will critically evaluate the effectiveness of methadone maintenance programs (MMP) in limiting the spread of the AIDS virus (HTLV III/LAV) among IVDU by retrospective and prospective comparisons of four groups of IVDU over 2-6 years. This long follow-up will allow description of the clinical course of HTLV III/LAV infection in very closely followed IVDU as well as expansion of the data base needed for an evaluation of factors predictive of clinical outcome. Preliminary studies show that 10% of a group of 283 New Haven IVDU were already infected with HTLV III/LAV in 1982-83. Therefore, this area may serve as a useful location to test the hypothesis that the rate of acquisition of HTLV III/LAV infection over time is less for a group on MMP than for IVDU not on drug treatment. The proposed study will re-evaluate up to 175 of the subjects for whom HTLV III/LAV antibody status in 1982-83 is known. Sixty-five of this 1982-83 cohort are currently on MMP and will be invited to participate in the study. The 110 subjects from the 1982-83 serum collection not currently on drug treatment in New Haven will be traced and invited to participate. Two other groups will be enrolled in 1986 and followed: 100 subjects who have been on MMP continuously since 1982 and 100 IVDU actively injecting drugs since 1982-83 invited to participate from consecutive admissions to the MMP. In addition, ongoing control seroprevalence data for those actively using injection drugs will be available from the State of Connecticut surveillance of all MMP admissions at selected drug treatment centers statewide (including New Haven after all new MMP entrants are enrolled in 1986). Evaluation of all subjects will include comprehensive medical evaluation, testing for HTLV III/LAV antibody with "western" blot confirmation, interview collection of behavioral data including drug injection, sexual and contraceptive practices, and cytomegalovirus and hepatitis B serologies. Seropositive subjects will have additional tests of immunologic function, HTLV III/LAV cultures and Epstein-Barr virus serologies. Comparison of the rate of increase in HTLV III/LAV antibody prevalence among those continuing in MMP to the rate of increase seen in active intravenous drug users over the same time will most directly test the hypothesis. Multivariate analysis with logistic regression modelling will provide a preliminary evaluation of predictors of outcome.